Influenza is a highly infectious acute respiratory viral disease that is characterized by recurrent annual epidemics and periodic major worldwide pandemics. Outbreaks are caused by infection of the highly diverse and mutable influenza viruses A and B (IFV A & IFV B). Novel broad-spectrum prophylaxis and therapeutics are critically needed to address the annual influenza epidemics and the escalating threat of pandemic influenza. NexBio has created a novel recombinant fusion protein-based anti-IFV agent, referred to as Fludase(r). Distinct from conventional vaccines and antivirals, Fludase(r) works by eliminating influenza virus receptors on the airway surface. It potentially confers broad-spectrum protection against all subtypes and strains of influenza viruses without the need for annual updates. Fludase(r) also has several built-in features to enable long drug retention on the airway surface and was engineered to be nonimmunogenic in humans. In the last 2 years, NexBio has finalized the molecular sequence of Fludase(r) and demonstrated its broad and potent anti-IFV efficacy in tissue culture and in two animal models. These accomplishments have provided strong justification for further developmental studies of Fludase(r). During the recent pre-IND meeting, the FDA raised several preclinical questions and indicated that as a first-in-class drug candidate, a thorough understanding of the Fludase(r) safety issues and mechanism of action is necessary. The main focus of this Challenge Grant proposal is to address the FDA's specific requests. Additionally, this grant proposal addresses new and important issues arising from Fludase(r) analytical and manufacture development. [unreadable] [unreadable] [unreadable]